Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Relapsed and Refractory Multiple Myeloma

An Open-label Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

This is a Phase 2 open-label study to evaluate the efficacy and safety of ibrutinib in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma.

Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoeitic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. Ibrutinib is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of ibrutinib in combination with bortezomib and dexamethasone in subjects with relapsed/relapsed and refractory multiple myeloma.

Inclusion Criteria:

• Subjects with multiple myeloma (MM) who have received 1-3 prior lines of therapy and have demonstrated disease progression since the completion of the most recent treatment regimen. (Subjects may have received prior bortezomib exposure if it does not meet the exclusion criteria for prior proteasome inhibitor use)

• Measurable disease defined by at least one of the following:

  • Serum monoclonal protein (SPEP) ≥1 g/dL (for subjects with immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE) or immunoglobulin M (IgM) multiple myeloma SPEP ≥0.5 g/dL)
  • Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine electrophoresis

• Adequate hematologic, hepatic and renal function

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

Exclusion Criteria:

• Subject must not have primary refractory disease
• Refractory or non-responsive to prior proteasome inhibitor (PI) therapy (bortezomib or carfilzomib)
• Peripheral neuropathy Grade ≥2 or Grade 1 with pain at Screening
• Plasma cell leukemia, primary amyloidosis, or POEMS syndrome
• Unable to swallow capsules or disease significantly affecting gastrointestinal function
• Requires treatment with strong CYP3A inhibitors
• Women who are pregnant or breast feeding